Environmental Factor, June 2010, National Institute of Environmental Health Sciences

GEMS Meeting Highlights Tox21

By Eddy Ball June 2010

Speaker Windy Boyd, left, sat with NTP colleague Kristine Witt during Xia's talk. Witt is part of the NTP High-Throughput Initiative and a longtime member and former officer of GEMS.
(Photo courtesy of Steve McCaw)

Following the first round of speakers, Xia, center, spoke with Little, right, and retired NIEHS scientist Errol Zeiger, Ph.D., J.D., who is now a freelance science writer.
(Photo courtesy of Steve McCaw)

French, left, said of the President's Council on Cancer report, "Maybe there'll be a renaissance," as researchers use HTS to identify biological pathways related to development of cancer. During the morning break, he chatted with NTP toxicologist Raj Chhabra, Ph.D.
(Photo courtesy of Steve McCaw)

Little, right, posed with Claxton and his Lifetime Achievement Award. In his acceptance presentation, Claxton shared what he called "pearls of wisdom" from his career as a principal investigator.
(Photo courtesy of Steve McCaw)

As the final speaker of the day, Judson brought a sense of closure to proceedings as he described accessible databases that can be queried as scientists tackle the enormous backlog of untested chemicals by identifying early-stage biological perturbations linked to disease endpoints.
(Photo courtesy of Steve McCaw)

During its spring meeting May 17 at the North Carolina Biotechnology Center, the Genetics and Environmental Mutagenesis Society (GEMS) (http://www.gems-nc.org/index.html) offered members an inside look at ongoing efforts to advance predictive toxicology. The event featured a line up of speakers from NIEHS and NTP, NIH Chemical Genomics Center (NCGC), U.S. Environmental Protection Agency (EPA), and Hamner Institutes.

While the meeting looked forward to the new toxicology of the 21st century with the theme "High-Throughput Screening (HTS) for Chemical Genomics and Computational Toxicology," members also had an opportunity to reflect on GEMS' 27 years as a professional society. Midway through the meeting, attendees enjoyed an entertaining and inspiring talk by Larry Claxton, Ph.D., a retired EPA principal investigator, who was honored with a Lifetime Achievement Award for his contributions as a founding member and president of GEMS.

The meeting opened with welcome remarks from GEMS President and NIEHS toxicologist Jef French, Ph.D., and GEMS President-elect and EPA toxicologist Stephen Little, who organized and moderated the meeting. In his remarks, French said of the program, "I think it's very timely." He also noted, "The more things change, the more they remain the same," as he referred to the recent report by the President's Council on Cancer underscoring the need for continued research on environmental exposures and chemicals in the etiology and progression of cancer.

As presenters at the meeting observed, advanced screening methods using in vitro samples and in vivo alternative models, such as nematodes and zebrafish, in combination with state-of-the-art bioinformatics support, are helping researchers build massive, accessible libraries of data on compounds to support the goals of Tox21 - a consortium created by NCGC, NIEHS/NTP, and EPA in a 2008 memorandum of understanding. This new, trans-agency collaboration is anticipated to generate data more relevant to humans; expand the number of chemicals that are tested; and reduce the time, money, and number of animals involved in toxicity testing.

The first speaker, Menghang Xia, Ph.D. (http://www.ncgc.nih.gov/about/mxia.html), group leader of Cellular Toxicity and Signaling at the NCGC, opened her talk on "Application of Quantitative High-Throughput Screening (qHTS) in Toxicological Studies at NCGC" with a review of developments that led up to the establishment of Tox21, especially the 2007 National Research Council report that called for a paradigm shift in toxicology testing. Xia described robot-assisted HTS using 1536-well plate format to screen as many as one million samples in seven days in the search for biochemical pathways in vitro that can predict adverse outcomes well in advance of traditional pathological endpoints.

The speakers who followed focused on components of the overall HTS and alternative method initiative and explained how their respective research agendas work in concert to promote the overall goals of Tox21 and the development of advanced predictive toxicology.

NIEHS WormTox Group (http://www.niehs.nih.gov/research/atniehs/labs/ltp/cg/index.cfm) Senior Research Assistant Windy Boyd, Ph.D., who discussed the use of nematodes as a model organism in a talk titled "Caenorhabditis elegans in Medium-Throughput Toxicological Testing"

EPA Toxicologist Steven Simmons, Ph.D., who explored efforts to use HTS to prioritize chemicals for more exhaustive testing based on activation of stress-response pathways in a talk on "Integrated Pathway Approach to High-Throughput Toxicant Identification and Characterization"

Hamner Institutes toxicologist Russell Thomas, Ph.D. (http://www.thehamner.org/translational-research/scientists/russell-thomas.html), who described his experiments with alternative mouse models in a talk titled "Experimentally Defining Toxicity Pathways Using In Vitro High-Content Screening of Embryonic Fibroblasts from the Mouse Diversity Panel"

EPA National Center for Computational Toxicology (NCCT) bioinformatician Richard Judson, Ph.D., who described advances in compiling two massive publicly available databases (http://www.epa.gov/ncct/) on compounds in a report on "ToxCast/ACTor HTS Informatics for Computational Toxicology Models"

As the meeting closed, attendees looked forward to another thought-provoking day-long meeting in the fall, which will also feature oral and poster presentations by students and trainees. GEMS fosters the training of the next generation of biomedical researchers through such professional development and travel awards to winners of the competition.

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